Radiolocalization of monoclonal antibodies in hepatic metastases from human colon cancer in congenitally athymic mice.
Intrasplenic injection of the HT-29 LMM metastatic human colon cancer line reproducibly results in hepatic metastasis formation in congenitally athymic mice. HT-29-15, a murine monoclonal antibody (mAb) of the IgG1 class reactive with the HT-29 LMM line, and BL-3, an isotype-matched control antibody, were labeled with 125I. Labeled mAbs were injected i.v. in mice with hepatic metastases, and animals were sacrificed on days 3, 5, and 7. Specific mAb uptake by tumor was significantly greater than nonspecific mAb uptake, as evidenced by specific/nonspecific tumor/blood ratios (radiolocalization indices) of 3.47/1-25.6/1. Relative mAb uptake was greater by the hepatic tumors than by the splenic tumors from day 3 to day 7, although this was significant (P less than 0.05) only on day 7 (5.12 +/- 2.97 versus 1.79 +/- 0.71). Tumor/uninvolved tissue ratios were also significantly greater (P less than 0.05) for the hepatic metastases than for the splenic tumors on day 7 (12.23 +/- 3.85 versus 6.63 +/- 2.63). This murine hepatic metastasis model appears useful for evaluation of localization of mAbs to hepatic metastases from human colon carcinoma.
Yoshida
K
K
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Rivoire
M
M
Divgi
C
C
Welt
S
S
Cohen
A M
AM
Sigurdson
E R
ER
D000818:Animals; D000911:Antibodies, Monoclonal; D003110:Colonic Neoplasms / Q000378:metabolism; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes